Association between the HLA-B*1502 gene and mild maculopapular exanthema induced by antiepileptic drugs in Northwest China

Abstract

Background The relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. In this study, we investigated the association between AED-induced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China. Methods We enrolled 165 subjects including nine patients with AED-MPE and 156 AED-tolerant patients as controls. HLA-B*1502 gene polymorphism was detected using digital fluorescence molecular hybridization (DFMH). The results of HLA genotyping were expressed as positive or negative for the HLA-B*1502 allele. An analysis of AED-MPE risk factors was performed using binary logistic regression, and differences in genotype frequencies between groups were assessed with the continuity correction chi-square test. Results We found that the HLA-B*1502 gene was a risk factor for AED-MPE (P = 0.028). The incidence of MPE induced by the two types of AEDs was different, and the incidence of aromatic AEDs use was higher that of non-aromatic AEDs use (P = 0.025). The comparison of the gene frequencies of the HLA-B*1502 allele between the two groups taking aromatic AEDs was also statistically significant (P = 0.045). However, there were no significant differences in terms of age, gender, ethnicity, or region in patients with MPE induced by AEDs. In addition, no association between the HLA-B1502 allele and CBZ- or OXC-induced MPE was found. Conclusions In northwestern China, the HLA-B*1502 allele was associated with aromatic AED-MPE. Since MPE can develop into Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the HLA-B*1502 gene should be evaluated before administering AEDs.

Associations of HLA genetic variants with carbamazepine‐induced cutaneous adverse drug reactions: An updated meta‐analysis

“… 1 , 5 , 6 Some studies also found an association between CBZ use and the development of MPE/DRESS. 7 , 8 , 9 , 10 …”

“…Although different medications such as allopurinol, phenytoin, abacavir, dapsone, flucloxacillin, and cotrimoxazole have been strongly associated with cADRs, carbamazepine (CBZ) is the most studied and causes SJS/TEN in a considerable proportion of patients 1,5,6 . Some studies also found an association between CBZ use and the development of MPE/DRESS 7–10 …”